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dc.contributor.authorMoerke, C
dc.contributor.authorJaco, I
dc.contributor.authorDewitz, C
dc.contributor.authorMueller, T
dc.contributor.authorJacobsen, A
dc.contributor.authorGautheron, J
dc.contributor.authorFritsch, J
dc.contributor.authorSchmitz, J
dc.contributor.authorBraesen, JH
dc.contributor.authorGuenther, C
dc.contributor.authorMurphy, JM
dc.contributor.authorKunzendorf, U
dc.contributor.authorMeier, P
dc.contributor.authorKrautwald, S
dc.date.accessioned2020-12-09T23:37:21Z
dc.date.available2020-12-09T23:37:21Z
dc.date.issued2019-09-01
dc.identifierpii: 10.1038/s41418-018-0232-2
dc.identifier.citationMoerke, C., Jaco, I., Dewitz, C., Mueller, T., Jacobsen, A., Gautheron, J., Fritsch, J., Schmitz, J., Braesen, J. H., Guenther, C., Murphy, J. M., Kunzendorf, U., Meier, P. & Krautwald, S. (2019). The anticonvulsive Phenhydan (R) suppresses extrinsic cell death. CELL DEATH AND DIFFERENTIATION, 26 (9), pp.1631-1645. https://doi.org/10.1038/s41418-018-0232-2.
dc.identifier.issn1350-9047
dc.identifier.urihttp://hdl.handle.net/11343/253279
dc.description.abstractDifferent forms of regulated cell death-like apoptosis and necroptosis contribute to the pathophysiology of clinical conditions including ischemia-reperfusion injury, myocardial infarction, sepsis, and multiple sclerosis. In particular, the kinase activity of the receptor-interacting serine/threonine protein kinase 1 (RIPK1) is crucial for cell fate in inflammation and cell death. However, despite its involvement in pathological conditions, no pharmacologic inhibitor of RIPK1-mediated cell death is currently in clinical use. Herein, we screened a collection of clinical compounds to assess their ability to modulate RIPK1-mediated cell death. Our small-scale screen identified the anti-epilepsy drug Phenhydan® as a potent inhibitor of death receptor-induced necroptosis and apoptosis. Accordingly, Phenhydan® blocked activation of necrosome formation/activation as well as death receptor-induced NF-κB signaling by influencing the membrane function of cells, such as lipid raft formation, thus exerting an inhibitory effect on pathophysiologic cell death processes. By targeting death receptor signaling, the already FDA-approved Phenhydan® may provide new therapeutic strategies for inflammation-driven diseases caused by aberrant cell death.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.titleThe anticonvulsive Phenhydan (R) suppresses extrinsic cell death
dc.typeJournal Article
dc.identifier.doi10.1038/s41418-018-0232-2
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.affiliation.department
melbourne.source.titleCell Death and Differentiation
melbourne.source.volume26
melbourne.source.issue9
melbourne.source.pages1631-1645
dc.rights.licenseCC BY
melbourne.elementsid1357440
melbourne.contributor.authorMurphy, James
melbourne.contributor.authorJacobsen, Annette
dc.identifier.eissn1476-5403
melbourne.accessrightsOpen Access


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